ABSTRACT ? Core C This PPG is a multidisciplinary investigation of in vivo and in vitro models of endosomal, autophagic, and lysosomal abnormalities in Alzheimer's disease (AD) considered critical to AD pathogenesis. This Core provides specialized services, required by at least three of the four Projects of the PPG. These services are best coordinated by a core to increase efficiencies of time and cost, promote scientific synergies, and maximally utilize dedicated highly specialized facilities. The specific aims of Core C are: (1) To acquire, store and efficiently distribute well-characterized tissues (brains and fibroblasts) from cases of AD, FAD, Trisomy 21 and non-demented and non-AD neurological controls (e.g., PD, HD) in a coordinated manner for studies in the PPG. Cultured primary mouse neurons and glial subtypes prepared under standardized conditions will be distributed routinely. (2) To perform electron microscopy and immunogold electron microscopy on cell/mouse models, human brains and isolated subcellular fractions including extracellular vesicles. (3) To perform ELISA to quantify A? and other APP metablolites in AD brains, brains of mouse models and media and lysates of fibroblasts and other cell models. (4) To provide specialized histological procedures, morphometric techniques, fluorescence/confocal applications and neurosurgical procedures as needed for all four Projects as well as provide training on laser confocal microscopy and video-fluorescent microscopy. (5). To maintain, distribute and purify polyclonal and monoclonal antibodies generated in-house. (6) To administer to mouse models behavioral assays of memory and motor performances from a highly standardized battery of validated tests. (7) To coordinate collaborations between investigators in the PPG and in Columbia University and NYULMC facilities for studies employing lipidomics, proteomics and RNA-sequencing technologies and maintain an accessible bank for the acquired data. The Core also provides standardized instructions for reagents (e.g., antibodies), cell culture conditions, procedures/methods, data capture/analysis to ensure reproducibility for the same method across the Projects. The Core serves all Projects and is essential to their success.